title: Angiotensin-(1-7) synergizes with colony-stimulating factors in hematopoietic recovery.
abstract: OBJECTIVE
  Angiotensin (1-7) [A(1-7)] is a bioactive peptide of the renin angiotensin system that stimulates the number of bone marrow progenitors and hematopoietic recovery after myelosuppression. We evaluated the combination of A(1-7) with colony-stimulating factors, Neupogen and Epogen, on bone marrow progenitors and the recovery of circulating formed elements following chemotherapy.
  
  
  METHODS
  Mice were injected with gemcitabine followed 2 days later with A(1-7). Circulating blood cells and bone marrow progenitors were measured over time.
  
  
  RESULTS
  Combination of A(1-7) with Neupogen (the latter given only 3 days starting at the white blood cell nadir) decreased the amount of Neupogen needed for optimal recovery by 10-fold. The progenitors measured include CFU-GEMM, CFU-GM, CFU-Meg and BFU-E. A(1-7) increased recovery of all progenitors when given alone or in combination with Neupogen above that with Neupogen alone. Combination of A(1-7) with Epogen slightly increased (not significantly) red blood cell concentrations above those achieved by Epogen alone. However, in this model, A(1-7) or A(1-7) in combination with Epogen increased all erythroid progenitors with the largest effect on early erythroid progenitors (immature BFU-E).
  
  
  CONCLUSIONS
  Neupogen and Epogen acted synergistically with A(1-7) to increase the concentration of myeloid, megakaryocytic and erythroid progenitor cells in the bone marrow following chemotherapy suggesting that A(1-7)'s multilineage effect on early progenitors in the marrow facilitates proliferation in response to lineage-specific growth factors.
authors.affiliation: Titus Family Clinical Pharmacy and Pharmaceutical Economics and Policy, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Room 530, Los Angeles, CA, 90089, USA, krodgers@pharmacy.usc.edu.
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Rodgers
authors.forename: Theresa B
authors.initials: TB
authors.lastname: Espinoza
authors.forename: Norma
authors.initials: N
authors.lastname: Roda
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Meeks
authors.forename: Gere S
authors.initials: GS
authors.lastname: diZerega
mesh_terms: D000803:Angiotensin I / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000633:toxicity; D004357:Drug Synergism; D000068817:Epoetin Alfa; D015672:Erythroid Precursor Cells / Q000187:drug effects / Q000378:metabolism; D004921:Erythropoietin / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D006397:Hematinics; D008533:Megakaryocytes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D023461:Myeloid Progenitor Cells / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D006397:Hematinics; D010446:Peptide Fragments; D011994:Recombinant Proteins; D003841:Deoxycytidine; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D000068817:Epoetin Alfa; D000803:Angiotensin I; C118790:angiotensin I (1-7); D000069585:Filgrastim; D000093542:Gemcitabine